R Flynn

Intensity-modulated x-ray (IMXT) versus proton (IMPT) therapy for theragnostic hypoxia-based dose painting

In this work the abilities of intensity-modulated x-ray therapy (IMXT) and intensity-modulated proton therapy (IMPT) to deliver boosts based on theragnostic imaging were assessed. Theragnostic imaging is the use of functional or molecular imaging data for prescribing radiation dose distributions. Distal gradient tracking, an IMPT method designed for the delivery of non-uniform dose distributions, was assessed. Dose prescriptions for a hypoxic region in a head and neck squamous cell carcinoma patient were designed to either uniformly boost the region or redistribute the dose based on positron emission tomography (PET) images of the (61)Cu(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) ((61)Cu-ATSM) hypoxia surrogate. Treatment plans for the prescriptions were created for four different delivery methods: IMXT delivered with step-and-shoot and with helical tomotherapy, and IMPT delivered with spot scanning and distal gradient tracking. IMXT and IMPT delivered comparable dose distributions within the boost region for both uniform and redistributed theragnostic boosts. Normal tissue integral dose was lower by a factor of up to 3 for IMPT relative to the IMXT. For all delivery methods, the mean dose to the nearby organs at risk changed by less than 2 Gy for redistributed versus uniform boosts. The distal gradient tracking method resulted in comparable plans to the spot scanning method while reducing the number of proton beam spots by a factor of over 3.

On the sensitivity of IMRT dose optimization to the mathematical form of a biological imaging-based prescription function

Voxel-based prescriptions of deliberately non-uniform dose distributions based on molecular imaging, so-called dose painting or theragnostic radiation therapy, require specification of a transformation that maps the image data intensities to prescribed doses. However, the functional form of this transformation is currently unknown. An investigation into the sensitivity of optimized dose distributions resulting from several possible prescription functions was conducted. Transformations between the radiotracer activity concentrations from Cu-ATSM PET images, as a surrogate of tumour hypoxia, and dose prescriptions were implemented to yield weighted distributions of prescribed dose boosts in high uptake regions. Dose escalation was constrained to reflect clinically realistic whole tumour doses and constant normal tissue doses. Optimized heterogeneous dose distributions were found by minimizing a voxel-by-voxel quadratic objective function in which all tumour voxels were given equal weight. Prescriptions based on a polynomial mapping function were found to be least constraining on their optimized plans, while prescriptions based on a sigmoid mapping function were the most demanding to deliver. A prescription formalism that fixed integral dose was less sensitive to errors in the choice of the mapping function than one that boosted integral dose. Integral doses to normal tissue and critical structures were insensitive to the shape of the prescription function. Planned target dose conformity improved with smaller beamlet dimensions until the inherent spatial resolution of the functional image was matched. Clinical implementation of dose painting depends on advances in absolute quantification of functional images and improvements in delivery techniques over smaller spatial scales.

Comparison of intensity modulated x-ray therapy and intensity modulated proton therapy for selective subvolume boosting: a phantom study

Selective subvolume boosting can theoretically improve tumour control probability while maintaining normal tissue complication probabilities similar to those of uniform dose distributions. In this work the abilities of intensity-modulated x-ray therapy (IMXT) and intensity-modulated proton therapy (IMPT) to deliver boosts to multiple subvolumes of varying size and proximities are compared in a thorough phantom study. IMXT plans were created using the step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) methods. IMPT plans were created with the spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT) methods. IMPT-DGT is a generalization of the distal edge tracking method designed to reduce the number of proton beam spots required to deliver non-uniform dose distributions relative to IMPT-SS. The IMPT methods were delivered over both 180 degrees and 360 degrees arcs. The IMXT-SAS and IMPT-SS methods optimally satisfied the non-uniform dose prescriptions the least and the most, respectively. The IMPT delivery methods reduced the normal tissue integral dose by a factor of about 2 relative to the IMXT delivery methods, regardless of the delivery arc. The IMPT-DGT method reduced the number of proton beam spots by a factor of about 3 relative to the IMPT-SS method.

A method for partial volume correction of PET-imaged tumor heterogeneity using expectation maximization with a spatially varying point spread function

Tumor heterogeneities observed in positron emission tomography (PET) imaging are frequently compromised by partial volume effects which may affect treatment prognosis, assessment or future implementations such as biologically optimized treatment planning (dose painting). This paper presents a method for partial volume correction of PET-imaged heterogeneous tumors. A point source was scanned on a GE Discovery LS at positions of increasing radii from the scanners center to obtain the spatially varying point spread function (PSF). PSF images were fit in three dimensions to Gaussian distributions using least squares optimization. Continuous expressions were devised for each Gaussian width as a function of radial distance, allowing for generation of the system PSF at any position in space. A spatially varying partial volume correction (SV-PVC) technique was developed using expectation maximization (EM) and a stopping criterion based on the methods correction matrix generated for each iteration. The SV-PVC was validated using a standard tumor phantom and a tumor heterogeneity phantom and was applied to a heterogeneous patient tumor. SV-PVC results were compared to results obtained from spatially invariant partial volume correction (SINV-PVC), which used directionally uniform three-dimensional kernels. SV-PVC of the standard tumor phantom increased the maximum observed sphere activity by 55 and 40% for 10 and 13 mm diameter spheres, respectively. Tumor heterogeneity phantom results demonstrated that as net changes in the EM correction matrix decreased below 35%, further iterations improved overall quantitative accuracy by less than 1%. SV-PVC of clinically observed tumors frequently exhibited changes of +/-30% in regions of heterogeneity. The SV-PVC method implemented spatially varying kernel widths and automatically determined the number of iterations for optimal restoration, parameters which are arbitrarily chosen in SINV-PVC. Comparing SV-PVC to SINV-PVC demonstrated that similar results could be reached using both methods, but large differences result for the arbitrary selection of SINV-PVC parameters. The presented SV-PVC method was performed without user intervention, requiring only a tumor mask as input. Research involving PET-imaged tumor heterogeneity should include correcting for partial volume effects to improve the quantitative accuracy of results.

On the impact of longitudinal breathing motion randomness for tomotherapy delivery.

The purpose of this study is to explain the unplanned longitudinal dose modulations that appear in helical tomotherapy (HT) dose distributions in the presence of irregular patient breathing. This explanation is developed by the use of longitudinal (1D) simulations of mock and surrogate data and tested with a fully 4D HT delivered plan. The 1D simulations use a typical mock breathing function which allows more flexibility to adjust various parameters. These simplified simulations are then made more realistic by using 100 surrogate waveforms all similarly scaled to produce longitudinal breathing displacements. The results include the observation that, with many waveforms used simultaneously, a voxel-by-voxel probability of a dose error from breathing is found to be proportional to the realistically random breathing amplitude relative to the beam width if the PTV is larger than the beam width and the breathing displacement amplitude. The 4D experimental test confirms that regular breathing will not result in these modulations because of the insensitivity to leaf motion for low-frequency dynamics such as breathing. These modulations mostly result from a varying average of the breathing displacements along the beam edge gradients. Regular breathing has no displacement variation over many breathing cycles. Some low-frequency interference is also possible in real situations. In the absence of more sophisticated motion management, methods that reduce the breathing amplitude or make the breathing very regular are indicated. However, for typical breathing patterns and magnitudes, motion management techniques may not be required with HT because typical breathing occurs mostly between fundamental HT treatment temporal and spatial scales. A movement beyond only discussing margins is encouraged for intensity modulated radiotherapy such that patient and machine motion interference will be minimized and beneficial averaging maximized. These results are found for homogeneous and longitudinal on-axis delivery for unplanned longitudinal dose modulations.

Dosimetric characterization and application of an imaging beam line with a carbon electron target for megavoltage cone beam computed tomography.

Imaging dose from megavoltage cone beam computed tomography (MVCBCT) can be significantly reduced without loss of image quality by using an imaging beam line (IBL), with no flattening filter and a carbon, rather than tungsten, electron target. The IBL produces a greater keV-range x-ray fluence than the treatment beam line (TBL), which results in a more optimal detector response. The IBL imaging dose is not necessarily negligible, however. In this work an IBL was dosimetrically modeled with the Philips Pinnacle3 treatment planning system (TPS), verified experimentally, and applied to clinical cases. The IBL acquisition dose for a 200 degrees gantry rotation was verified in a customized acrylic cylindrical phantom at multiple imaging field sizes with 196 ion chamber measurements. Agreement between the measured and calculated IBL dose was quantified with the 3D gamma index. Representative IBL and TBL imaging dose distributions were calculated for head and neck and prostate patients and included in treatment plans using the imaging dose incorporation (IDI) method. Surface dose was measured for the TBL and IBL for four head and neck cancer patients with MOSFETs. The IBL model, when compared to the percentage depth dose and profile measurements, had 97% passing gamma indices for dosimetric and distance acceptance criteria of 3%, 3 mm, and 100% passed for 5.2%, 5.2 mm. For the ion chamber measurements of phantom image acquisition dose, the IBL model had 93% passing gamma indices for acceptance criteria of 3%, 3 mm, and 100% passed for 4%, 4 mm. Differences between the IBL- and TBL-based IMRT treatment plans created with the IDI method were dosimetrically insignificant for both the prostate and head and neck cases. For IBL and TBL beams with monitor unit values that would result in the delivery of the same dose to the depth of maximum dose under standard calibration conditions, the IBL imaging surface dose was higher than the TBL imaging surface dose by an average of 18%, with a standard deviation of 8% (p = 2 x 10(-6)). The IBL can be modeled with acceptable accuracy using a standard TPS, and accounting for IBL dose in treatment plans with the IDI method is straightforward. The resulting composite dose distributions, assuming similar imaging doses, are negligibly different from those of the TBL. The increased IBL surface dose relative to the TBL is likely clinically insignificant.

A dynamic collimation system for penumbra reduction in spot-scanning proton therapy: Proof of concept

PURPOSE In the absence of a collimation system the lateral penumbra of spot scanning (SS) dose distributions delivered by low energy proton beams is highly dependent on the spot size. For current commercial equipment, spot size increases with decreasing proton energy thereby reducing the benefit of the SS technique. This paper presents a dynamic collimation system (DCS) for sharpening the lateral penumbra of proton therapy dose distributions delivered by SS. METHODS The collimation system presented here exploits the property that a proton pencil beam used for SS requires collimation only when it is near the target edge, enabling the use of trimmers that are in motion at times when the pencil beam is away from the target edge. The device consists of two pairs of parallel nickel trimmer blades of 2 cm thickness and dimensions of 2 cm×18 cm in the beams eye view. The two pairs of trimmer blades are rotated 90° relative to each other to form a rectangular shape. Each trimmer blade is capable of rapid motion in the direction perpendicular to the central beam axis by means of a linear motor, with maximum velocity and acceleration of 2.5 m/s and 19.6 m/s2, respectively. The blades travel on curved tracks to match the divergence of the proton source. An algorithm for selecting blade positions is developed to minimize the dose delivered outside of the target, and treatment plans are created both with and without the DCS. RESULTS The snout of the DCS has outer dimensions of 22.6×22.6 cm2 and is capable of delivering a minimum treatment field size of 15×15 cm2. Using currently available components, the constructed system would weigh less than 20 kg. For irregularly shaped fields, the use of the DCS reduces the mean dose outside of a 2D target of 46.6 cm2 by approximately 40% as compared to an identical plan without collimation. The use of the DCS increased treatment time by 1-3 s per energy layer. CONCLUSIONS The spread of the lateral penumbra of low-energy SS proton treatments may be greatly reduced with the use of this system at the cost of only a small penalty in delivery time.

The impact of linac output variations on dose distributions in helical tomotherapy

It has been suggested for quality assurance purposes that linac output variations for helical tomotherapy (HT) be within +/-2% of the long-term average. Due to cancellation of systematic uncertainty and averaging of random uncertainty over multiple beam directions, relative uncertainties in the dose distribution can be significantly lower than those in linac output. The sensitivity of four HT cases with respect to linac output uncertainties was assessed by scaling both modeled and measured systematic and random linac output uncertainties until a dose uncertainty acceptance criterion failed. The dose uncertainty acceptance criterion required the delivered dose to have at least a 95% chance of being within 2% of the planned dose in all of the voxels in the treatment volume. For a random linac output uncertainty of 5% of the long-term mean, the maximum acceptable amplitude of the modeled, sinusoidal, systematic component of the linac output uncertainty for the four cases was 1.8%. Although the measured linac output variations represented values that were outside of the +/-2% tolerance, the acceptance criterion did not fail for any of the four cases until the measured linac output variations were scaled by a factor of almost three. Thus, the +/-2% tolerance in linac output variations for HT is a more conservative tolerance than necessary.

Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system.

PURPOSE To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd(2)O(2)S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si) flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL produces a greater fluence of keV-range photons than the TBL, to which the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB. METHODS A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVision(TM) image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head- and pelvis-sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast-to-noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data. RESULTS For head and neck and pelvis-sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10(- 8)), 1.64 (p < 10(- 13)), 2.66 (p < 10(- 9)), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head- and pelvis-sized phantoms. CONCLUSIONS Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose.

On the making of sharp longitudinal dose profiles with helical tomotherapy

Since the beam width on the helical tomotherapy machine produced by TomoTherapy Inc., is typically a few centimeters in the longitudinal direction (into the bore), the optimizer must choose to have a relatively high intensity local to the inside edge of a tumor or planning treatment volume (PTV) when avoiding an immediately adjacent organ at risk (OAR), either superior or inferior. By using a standalone version of the TomoTherapy dose calculator, a realistic beam is applied to idealized deconvolution schemes including the MATLAB Optimizer Toolbox for a simple one-dimensional PTV with adjacent OARs. The results are compared to a clinical example on the TomoTherapy planning station. It is learned that a Gibbs phenomenon type of oscillation in the dose within the tumor under these special circumstances is not unique to TomoTherapy, but is related to the attempt to form a sharp dose gradient-sharper than the beam profile with typical optimization constraints set to achieve a uniform dose as close as possible to the prescription. The clinical implication is that the Gibbs-induced cold spots force the dose to increase in the PTV if a typical PTV dose-volume constraint is used. It is recommended that the dose prescription be smoothed prior to optimization or the dosimetric goals for an OAR adjacent to the PTV are such that a sharp dose falloff is not demanded, especially if the user reduces the requirements that such an OAR be of both high importance and immediately adjacent to the PTV edge.